Silver(I) Triflate‐Catalyzed Protocol for the Post‐Ugi Synthesis of Spiroindolines

Abstract

A silver(I) triflate‐catalyzed protocol for the post‐Ugi synthesis of tetracyclic spiroindolines has been developed. The protocol worked best for indole‐3‐carbaldehyde‐derived Ugi adducts obtained using anilines and 3‐aryl propiolic acids. Thus, it is complementary to the previous cationic gold‐catalyzed procedure that was developed for analogues Ugi substrates derived from aliphatic amines and 3‐alkyl propiolic acids. Furthermore, we have demonstrated that under our new settings this domino Friedel‐Crafts ipso cyclization / imine trapping process could be efficiently combined with the preceding four‐component Ugi reaction into a two‐step one‐pot transformation.

Heteroarene‐tethered Functionalized Alkyne Metamorphosis

“…Absence of acid in the reaction medium suppressed the imine trapping step resulted in the formation of tricyclicindolenines (Scheme132). [153] Later,m icrowave-assisted,A u-nanoparticles supported on Al-SBA15c atalyzed transformation of Ugi-adduct 531 to corresponding spiro-indolines 534 was demonstrated by the same group. Using EtOH as solventat1 10 8C, terminal alkyne bearing substrates furnished the desired products in good to excellent yields whereas bulky substitution on amide nitrogen resulted poor yields.…”

“…Absence of acid in the reaction medium suppressed the imine trapping step resulted in the formation of tricyclic indolenines (Scheme 132). [153] …”

A DFT study on gold-catalyzed domino cyclization for post-Ugi synthesis of spiroindolines: insights on the origin of remarkable diastereoselectivity

“…22 Among them, the van der Eycken group made elegant achievements in multicomponent reactions in drug discovery and medical, and there is no dedicated mechanistic understanding on this topic, especially with regard to the relationship between the electronic properties of the substrates and the stereochemistry of the reaction. 23 The four-component Ugi reaction represents one of the highly important platforms to access a variety of precursors for diversity-oriented synthesis. It allows a rapid introduction of precondition suitable functional groups in the obtained Ugi precursors, serving as a compelling diversification device for constructing countless heterocycles in an effective manner, which is highly significant during screenings in drug discovery.…”

One-pot synthesis of natural-product inspired spiroindolines with anti-cancer activities

“…7 In the synthesized spiroindolines I–III compounds (Fig. 1), 8 spiroindolines II and III were prepared via a post-Ugi cascade reaction in two steps. Notably, these MCRs enabled new C–N and C–C bonds to be formed simultaneously, 9 suggesting that MCRs can serve as an effective tool for the preparation of functionalized spiroindoline analogues.…”